title: Apelin-13 limits infarct size and improves cardiac postischemic mechanical recovery only if given after ischemia.
abstract: We studied whether apelin-13 is cardioprotective against ischemia/reperfusion injury if given as either a pre- or postconditioning mimetic and whether the improved postischemic mechanical recovery induced by apelin-13 depends only on the reduced infarct size or also on a recovery of function of the viable myocardium. We also studied whether nitric oxide (NO) is involved in apelin-induced protection and whether the reported ischemia-induced overexpression of the apelin receptor (APJ) plays a role in cardioprotection. Langendorff-perfused rat hearts underwent 30 min of global ischemia and 120 min of reperfusion. Left ventricular pressure was recorded. Infarct size and lactate dehydrogenase release were determined to evaluate the severity of myocardial injury. Apelin-13 was infused at 0.5 μM concentration for 20 min either before ischemia or in early reperfusion, without and with NO synthase inhibition by N(G)-nitro-l-arginine (l-NNA). In additional experiments, before ischemia also 1 μM apelin-13 was tested. APJ protein level was measured before and after ischemia. Whereas before ischemia apelin-13 (0.5 and 1.0 μM) was ineffective, after ischemia it reduced infarct size from 54 ± 2% to 26 ± 4% of risk area (P < 0.001) and limited the postischemic myocardial contracture (P < 0.001). l-NNA alone increased postischemic myocardial contracture. This increase was attenuated by apelin-13, which, however, was unable to reduce infarct size. Ischemia increased APJ protein level after 15-min perfusion, i.e., after most of reperfusion injury has occurred. Apelin-13 protects the heart only if given after ischemia. In this protection NO plays an important role. Apelin-13 efficiency as postconditioning mimetic cannot be explained by the increased APJ level.
authors.affiliation: Dipartimento di Scienze Cliniche e Biologiche, Facoltà di Medicina e Chirurgia "S. Luigi Gonzaga", Regione Gonzole 10, 10043 Orbassano (TO) Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Rastaldo
authors.forename: Sandra
authors.initials: S
authors.lastname: Cappello
authors.forename: Anna
authors.initials: A
authors.lastname: Folino
authors.forename: Giovanni N
authors.initials: GN
authors.lastname: Berta
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Sprio
authors.forename: Gianni
authors.initials: G
authors.lastname: Losano
authors.forename: Michele
authors.initials: M
authors.lastname: Samaja
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pagliaro
mesh_terms: D000818:Animals; D000075244:Apelin Receptors; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D023421:Models, Animal; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000075244:Apelin Receptors; C491284:Aplnr protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; C495199:apelin-13 peptide; D009569:Nitric Oxide